Fentanyl and fentanyl analog derivatives such as sulfentanyl, carfentanyl, lofentanyl, and alfentanyl are extremely active analgesics. Their low dosage and their physicochemical properties such as, for example, the n-octanol/water partition coefficient, the melting point, and the molecular weight make it possible to supply the substances transdermally in an effective amount, and their pharmacokinetic properties such as the rapid metabolization and the relatively narrow therapeutic index make their transdermal supply desirable.
Indeed, for a number of years a fentanyl TTS has been on the market. This system is of the type known as a reservoir system. A reservoir system is a TTS which contains the active substance in a liquid or gel formulation in a pouch formed from an impermeable film and a membrane which is permeable for the active substance. The impermeable film acts as a backing layer, in order to prevent the liquid or gel formulation of the active substance emerging on the side of the pouch facing away from the skin. The membrane serves to regulate the rate of active substance release from the skin-facing side of the pouch. On this side, the membrane additionally possesses an adhesive layer for attaching the overall TTS to the skin.
In this specific case (Durogesic® TTS), fentanyl is in solution in a mixture of ethanol and water. Further details of this system can be found in U.S. Pat. No. 4,588,580 or DE 35 26 339, both of which contain a detailed description.
However, reservoir systems have a major disadvantage, namely that in the event of a leak (e.g., a simple mechanically induced damage, a cut or tear, splitting of the weld seam, etc.) in the pouch containing the active substance formulation, the active substance may come into contact with the skin over a large area and, as a consequence of this contact, may be absorbed in, excessive doses. Especially in the case of fentanyl and the fentanyl analog derivatives, this is potentially fatal, since overdose leads very rapidly to respiratory depression and hence fatal incidents. A number of such fatal or near-fatal incidents have been described in Clinical Pharmacokint.. 2000, 38 (1), 59-89.